Local electric and ionic changes in the muscle cell initiate many of the metabolic events that occur in this tissue during exercise. On the other hand, muscle metabolism during exercise is also influenced by a number of hormonal and nutritional factors. The proposed studies will examine the role of three such factors--insulin, the catechol amines and free fatty acids and ketone bodies. Three hypotheses will be tested: (1) That enhances insulin binding accounts for the increased uptake of glucose by muscle during the recovery period after exercise and possibley exercise itself; (2) That fatty acids and ketone bodies restrain the utilization of glucose and glucogen by muscle during exercise and enhance glycogen formation during the recovery period; and (3) That catechol amines, and particularly those from the adrenal medulla play a key role in regulating glycogenolysis and other metabolic events in exercising muscle. In addition, we will explore the basis for the insulin resistance of diabetic ketoacidosis and the inability of exercise to stimulate glucose transport in this condition. Insulin binding will be studied in the incubated rat soleus muscle and other investigations in either the isolated perfused rat hindquarter or intact rats. These studies should provide fundamental information about the metabolic response of skeletal muscle during exercise and recovery, the hormonal factors that control this response, and the relationship between insulin binding and its biological effect. In addition, they should clarify the role of fatty acids and ketone bodies in modulating muscle glucose and glycogen metabolism.